Selenium is a possible cancer preventive agent, and is being considered for use in intervention trials. A study in collaboration with the Cancer Prevention Studies Branch (ZO1 CN 00101-06 CPSB) is in progress which will provide information on the pharmacokinetics of selenium in its prototype forms -- sodium selenite (inorganic form) and selenomethionine (organic form). This information is unavailable for these agents in the dose currently considered optimal, and is necessary to the determination of time and manner of administration. Parameters such as percent absorption, maximum concentration, time to maximum concentration and mean residence times will be estimated for a single dose and compared in fasting and non-fasting subjects. In order to interpret the study data more fully, development of integrated kinetic models, one for selenite and one for selenomethionine is underway. Such models are useful in making inferences about drug metabolism and about the distribution of the drug in various body pools. A model of selenite has been developed based on pilot study data and tested on data from the main study. Various body pools have been hypothesized, and rates of exchange between them estimated, as well as mean residence times. Preliminary comparisons of rate constants for subjects when fasting and when non-fasting suggests that fasting status modulates the appearance of selenite in the plasma and that there is a greater first pass effect when the dose is given with food. Another aspect of the project is an analysis of variations in total selenium levels in the plasma, urine and feces both within and between individuals. This information is important in deciding what measures can be used to determine selenium status.